Cutting edge: Association with IκB Kinase β regulates the subcellular localization of Homer3

The signaling and adaptor protein Homer3 plays a role in controlling immune homeostasis and self-reactivity. Homer3 is recruited to the immune synapse (IS) following TCR ligation, although the mechanisms regulating this subcellular localization are unknown.We show that Homer3 specifically associates with a novel ubiquitin-like domain in the IκB kinase (IKK) β subunit of the IKK complex. Homer3 associates with IKKb in T cells and colocalizes with the IKK complex at the IS. However, Homer3 is not required for IKK activation, as NF-κB signaling is intact in Homer3-deficient T cells. Instead, the IKK complex recruits Homer3 to the IS following TCR engagement, and we present evidence that this association regulates actin dynamics in T cells. These findings identify a novel interaction between two major signaling proteins and reveal an unexpected NF-κB - independent function for the IKK complex in regulating the subcellular localization of Homer3.